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CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor
cells
S Aigner, ZM Sthoeger, M Fogel, E Weber, J Zarn, M Ruppert, Y Zeller, D Vestweber, R Stahel, M Sammar and P Altevogt
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
P-selectin (CD62P) is a Ca2+-dependent endogenous lectin that can be
expressed by vascular endothelium and platelets. The major ligand for P-
selectin on leukocytes is P-selectin glycoprotein ligand-1 (PSGL-1). P-
selectin can also bind to carcinoma cells, but the nature of the ligand(s)
on these cells is unknown. Here we investigated the P- selectin binding to
a breast and a small cell lung carcinoma cell line that are negative for
PSGL-1. We report that CD24, a mucin-type
glycosylphosphatidylinositol-linked cell surface molecule on human
neutrophils, pre B lymphocytes, and many tumors can promote binding to
P-selectin. Latex beads coated with purified CD24 from the two carcinoma
cell lines but also neutrophils could bind specifically to P- selectin-IgG.
The binding was dependent on divalent cations and was abolished by
treatment with O-sialoglycoprotein endopeptidase but not endoglycosidase F
or sialidase. The beads were stained with a monoclonal antibody (MoAb) to
CD57 (HNK-1 carbohydrate epitope) but did not react with MoAbs against the
sialylLe(x/a) epitope. The carcinoma cells and CD24-beads derived from
these cells could bind to activated platelets or P-selectin transfected
Chinese hamster ovary cells (P-CHO) in a P-selectin-dependent manner and
this binding was blocked by soluble CD24. Transfection of human
adenocarcinoma cells with CD24 enhanced the P-selectin-dependent binding to
activated platelets. Treatment of the carcinoma cells or the CD24
transfectant with phosphatidylinositol-specific phospholipase C reduced
CD24 expression and P-selectin-IgG binding concomitantly. These results
establish a role of CD24 as a novel ligand for P-selectin on tumor cells.
The CD24/P-selectin binding pathway could be important in the dissimination
of tumor cells by facilitating the interaction with platelets or
endothelial cells.
Volume 89,
Issue 9,
pp. 3385-3395,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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